Abstract TP332: Differential Functional Impact of Contralesional Motor Pathway Enhancement After Stroke: Insights From TMS, fMRI, and DTI

Introduction: Emerging evidence suggests that ipsilaterally descending motor pathways from the contralesional hemisphere to the lower limb may be enhanced after stroke. However, methodological limitations have restricted interpretation of whether these pathways are functionally enhanced, and evidence remains ambivalent about whether they aid recovery. The primary purpose of this study was to determine the relative enhancement of contralesional motor pathways to the paretic lower limb using a multi-dimensional estimate derived from transcranial magnetic stimulation (TMS), functional magnetic resonance imaging (fMRI), and diffusion tensor imaging (DTI). The secondary purpose was to examine associations between this composite estimate and lower limb motor control and coordination. Methods: Thirty-three individuals with chronic stroke [60.7 ± 8.3 years; 24 male, 9 female; 8.6 ± 6.6 years post-stroke] underwent TMS, fMRI, and DTI testing. For TMS, corticomotor excitability of the ipsilesional (contralateral) and contralesional (ipsilateral) hemisphere to the paretic lower limb was assessed. For fMRI, brain activation volume in each hemisphere was measured during paretic ankle dorsiflexion and plantarflexion. For DTI, fiber volume in each corticospinal tract was quantified. For each modality, the relative excitability/activation/volume of the contralesional hemisphere was calculated, and a single average composite was derived. Associations between individual measures and the composite with lower limb function (motor impairment, walking speed and endurance, interlimb coordination) were tested. Results: Across TMS, fMRI, and DTI, contralesional pathways were enhanced relative to ipsilesional pathways. The composite value was not correlated with lower limb function in the overall cohort. However, in individuals with low lesion load, better function was associated with less relative enhancement of contralesional pathways. In contrast, in those with high lesion load, better function was associated with greater relative enhancement of these pathways. Conclusions: Multi-modal evidence indicates that contralesional pathways to the paretic lower limb are enhanced after stroke. The functional relevance of this enhancement depends on lesion severity, with potential benefits in individuals with extensive ipsilesional pathway damage. These findings may inform individualized strategies for lower limb rehabilitation after stroke.